3-[4-(3-Fluorophenyl)-10-methyl-5-oxo-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-7-yl]benzonitrile | 635324-90-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-[4-(3-Fluorophenyl)-10-methyl-5-oxo-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-7-yl]benzonitrile
• 英文别名: 3-[4-(3-fluorophenyl)-10-methyl-5-oxo-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-7-yl]benzonitrile
• CAS: 635324-90-2
• 化学式: C₂₁H₁₃FN₆O
• 分子量: 384.372
• InChiKey: MZBCNTIPBPFKKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  29.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  92.29
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3-[4-(3-Fluorophenyl)-10-methyl-5-oxo-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-7-yl]benzonitrile 在 双氧水 、 potassium carbonate 作用下， 以 乙二醇 、 二甲基亚砜 为溶剂， 反应 4.0h， 以40%的产率得到3-[4-(3-Fluorophenyl)-10-methyl-5-oxo-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-7-yl]benzamide
  参考文献：
  名称：

  Structure–activity studies of a series of dipyrazolo[3,4- b :3′,4′- d ]pyridin-3-ones binding to the immune regulatory protein B7.1

  摘要：

  The interaction of co-stimulatory molecules on T cells with 137 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00183-4
• 作为产物：
  描述：

  3-(3-氰基苯基)-3-氧代丙酸甲酯 在 sodium hydride 、 溶剂黄146 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 正己烷 、 乙腈 为溶剂， 反应 12.0h， 生成 3-[4-(3-Fluorophenyl)-10-methyl-5-oxo-3,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-7-yl]benzonitrile
  参考文献：
  名称：

  Structure–activity studies of a series of dipyrazolo[3,4- b :3′,4′- d ]pyridin-3-ones binding to the immune regulatory protein B7.1

  摘要：

  The interaction of co-stimulatory molecules on T cells with 137 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00183-4